Abstract

BACKGROUND:

Recently, a new livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) Sequence Type 398 (ST398) isolate has emerged worldwide. Although there have been reports of invasive disease in humans, MRSA ST398 colonization is much more common in livestock and demonstrates especially high prevalence rates in pigs and calves. The aim of this study was to compare the genome sequence of an ST398 MRSA isolate with other S. aureus genomes in order to identify genetic traits that may explain the success of this particular lineage. Therefore, we determined the whole genome sequence of S0385, an MRSA ST398 isolate from a human case of endocarditis.

RESULTS:

The entire genome sequence of S0385 demonstrated considerable accessory genome content differences relative to other S. aureus genomes. Several mobile genetic elements that confer antibiotic resistance were identified, including a novel composite of an type V (5C2&5) Staphylococcal Chromosome Cassette mec (SCCmec) with distinct joining (J) regions. The presence of multiple integrative conjugative elements combined with the absence of a type I restriction and modification system on one of the two nuSa islands, could enhance horizontal gene transfer in this strain. The ST398 MRSA isolate carries a unique pathogenicity island which encodes homologues of two excreted virulence factors; staphylococcal complement inhibitor (SCIN) and von Willebrand factor-binding protein (vWbp). However, several virulence factors such as enterotoxins and phage encoded toxins, including Panton-Valentine leukocidin (PVL), were not identified in this isolate.

CONCLUSIONS:

Until now MRSA ST398 isolates did not cause frequent invasive disease in humans, which may be due to the absence of several common virulence factors. However, the proposed enhanced ability of these isolates to acquire mobile elements may lead to the rapid acquisition of determinants which contribute to virulence in human infections.

Compairison of the integrative conjugative elements. Amino acid matches from the six-frame translations (TBLASTX) of integrative conjugative elements of S. aureus S0385 (ICESa2 and ICESa1), B. subtilis (ICEBs1) [GenBank: AL009126 ] and L. monocytogenes (ICELm1) [GenBank: AARQ] dislayed using ACT http://www.sanger.ac.uk/software/ACT. ORFs are represented by coloured boxes. The red bars indicate TBLASTX matches between the elements. There are six proteins that are conserved among all ICEs (SAPIG0075, 0076, 0077 and 0079-0081), which include the FtsK/spoIII and replication initiation proteins.

Compairison of the SaPI. Nucleotide matches of SaPIbov, SaPI-S0385 and SaPI5 of S. aureus ET3, S0385 and USA300 FPR3757, respectivly dislayed using ACT. ORFs are represented by coloured boxes. The red bars indicate BLASTN matches between the elements, which mainly concern regions encoding genes that are essential for SAPI replication. The unique region in SaPI-S0385 contains the scn and vwb genes.